U.S. patent number 4,183,952 [Application Number 05/641,729] was granted by the patent office on 1980-01-15 for antimicrobial compositions.
Invention is credited to Edwin B. Michaels.
United States Patent |
4,183,952 |
Michaels |
January 15, 1980 |
Antimicrobial compositions
Abstract
There is provided an antimicrobial composition of low toxicity
having enhanced gram positive and gram negative activity and
consists essentially of: (a) an alkyl-N-sulfobetaine (0.1 part-40.0
parts, by weight), (b) an alkyl-N,N-dimethylamine oxide, an
alkyl-N,N-dihydroxyethylamine oxide, or an acylamido t-amine oxide
(0.1 part-40.0 parts, by weight), and (c) a protonating agent, such
as hydrochloric acid, acetic acid, in an amount sufficient to
adjust the pH of the overall composition to about 5.5 or below. The
composition exhibits skin degerming, cleansing, and deodorizing
properties and, particularly, its use exhibits long term inhibition
of body odor.
Inventors: |
Michaels; Edwin B. (East
Norwalk, CT) |
Family
ID: |
24573614 |
Appl.
No.: |
05/641,729 |
Filed: |
December 18, 1975 |
Current U.S.
Class: |
514/556; 424/65;
510/131; 510/137; 510/382; 510/383; 510/426; 510/433; 510/477;
510/494; 510/503 |
Current CPC
Class: |
A01N
33/24 (20130101); A01N 37/20 (20130101); A01N
37/44 (20130101); A01N 37/46 (20130101); A01N
41/04 (20130101); A61K 8/40 (20130101); A61K
8/44 (20130101); A61K 31/205 (20130101); A61Q
5/02 (20130101); A61Q 15/00 (20130101); A61Q
17/005 (20130101); A61Q 19/10 (20130101); C11D
1/75 (20130101); C11D 1/94 (20130101); C11D
3/0068 (20130101); C11D 3/48 (20130101); A01N
37/20 (20130101); A01N 37/46 (20130101); A01N
41/04 (20130101); A01N 2300/00 (20130101); A01N
2300/00 (20130101); A01N 2300/00 (20130101) |
Current International
Class: |
A01N
37/20 (20060101); A01N 37/44 (20060101); A01N
33/00 (20060101); A01N 33/24 (20060101); A01N
41/00 (20060101); A01N 37/46 (20060101); A01N
41/04 (20060101); A61K 31/185 (20060101); A61K
31/205 (20060101); C11D 1/88 (20060101); C11D
1/75 (20060101); C11D 1/94 (20060101); C11D
3/00 (20060101); C11D 3/48 (20060101); A61K
031/205 () |
Field of
Search: |
;424/316,320,325,329,65
;252/106 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Kirk-Othmer Encyc. of Chem. Tech., vol. 19 (1969), pp.
555-557..
|
Primary Examiner: Turner; V. D.
Claims
I claim:
1. A broad spectrum antimicrobial composition having low toxicity
which consists essentially of:
(a) 0.1 to 40 parts, by weight, of a higher alkyl-N-betaine said
betaine having the structure: ##STR3## where R is a higher alkyl of
from 10 to 18 carbon atoms, (b) 0.1 to 40 parts, by weight, of a
higher alkyl-N,N-dimethylamine oxide, a higher
alkyl-N,N-dihydroxyethylamine oxide, or an acylamido t-amine oxide
having the respective structure: ##STR4## where R.sub.1 is a higher
alkyl of from 10 to 18 carbon atoms, or mixtures of the same,
and
(c) a protonating agent, sufficient to adjust the pH of said
composition from 4 to 5.5.
2. The composition according to claim 1 wherein the alkyl-N-betaine
is coco-N-sulfobetaine.
3. The composition according to claim 1 wherein the alkyl-N-betaine
is stearyl-N-sulfobetaine.
4. The composition according to claim 1 wherein the higher
alkylamine oxide is coco-N,N-dimethylamine oxide.
5. The composition according to claim 1 wherein the higher
alkylamine oxide is stearyl-N,N-dihydroxyethylamine oxide.
6. The composition according to claim 1 wherein the protonating
reagent is citric acid.
7. The broad spectrum, antimicrobial composition according to claim
1 wherein the protonating reagent is acetic acid.
8. The composition according to claim 1 wherein the composition is
dissolved in an aqueous medium and wherein the pH of the aqueous
mixture is adjusted to and maintained at from 4.7 to 5.2.
Description
The present invention relates to antimicrobial compositions of
enhanced efficacy and safety. More particularly, the invention
relates to antimicrobial compositions having low toxicity and broad
spectrum antimicrobial activity comprising certain amphoteric
surfactants which per se have limited antimicrobial use. Still more
particularly, the invention is concerned with antimicrobial
compositions of enhanced gram positive and gram negative activity
consisting essentially of in admixture:
(a) an alkyl-N-sulfobetaine (0.1-40.0 parts, by weight),
(b) an alkyl-N,N-dimethylamine oxide, an
alkyl-N,N-dihydroxyethylamine oxide, or an acylamido t-amine oxide
(0.1-40.0 parts, by weight), and
(c) a protonating agent, such as hydrochloric acid, acetic acid or
citric acid in an amount sufficient to adjust the pH of the overall
composition to about 5.5, or below.
The compositions of the present invention exhibit sustained periods
of antimicrobial activity, particularly in the control of body
odor.
As is known, an outstanding method for the control of body odor is
to thoroughly wash the body with soap, but so prolific are the
microbial flora of the skin that distinctive malodors tend to
return within several hours after washing. To provide longer
periods of protection, there have been developed compositions which
either contain (a) astringents, such as aluminum chlorohydrate,
that inhibit apocrine and eccrine gland secretions or contain (b)
antimicrobial agents, such as hexachlorophene and
trichlorocarbanilamide. Unfortunately, astringent compositions have
limited value, since they have little or no control of microbial
decomposition of debris and uncontrolled secretions and where there
is control of secretions, such use suffers from severe shortened
periods so as to obtain effective control. Nonetheless, the latter
antimicrobial compositions have enjoyed widespread use.
Nonetheless, there have been recent investigations into topical and
systemic toxicity of the hereinabove named germicides used to
control body odor. These investigations have led to severe
restrictions, for instance, on the utilization of hexachlorophene
and the recognition of the dangers of other germicides. Further,
the use of astringents have only limited utility usually due to its
harsh action on skin, particularly, on those who have sensitive
skin. If a safe and effective antimicrobial composition of low
toxicity could be provided which would inhibit the development of
body odor for relatively long periods of time, eg., at least
twenty-four (24) hours, or longer, such a composition would satisfy
a real need in the art.
It is a principal object of the invention to provide an
antimicrobial composition of enhanced efficacy and safety which
possesses broad spectrum activity in combating body odor and
topical infections. It is a further object of the invention to
provide an antimicrobial composition comprising at least an
alkyl-N-sulfobetaine surfactant and an alkyl-N,N-dimethylamine
oxide, and acylamido t-amine oxide, or an
alkyl-N,N-dihydroxyethylamine oxide adjusted to a pH of 5.5, or
below, so as to control gram positive bacteria, gram negative
bacteria, fungi, and yeast, when topically applied. Other objects
and advantages will become apparent from a consideration of the
ensuing description.
According to the invention, there are provided antimicrobial
compositions comprising a mixture of (a) an alkyl-N-sulfobetaine
and (b) an alkyl-N,N-dimethylamine oxide, an acylamido t amine
oxide, or an alkyl-N,N-dihydroxyethylamine oxide. The components
are admixed at a temperature ranging from about 25.degree. C. to
80.degree. C. in a substantially aqueous or non-aqueous environment
and adjusted to a pH of 5.5, or below, to provide a substantially
uniform homogeneous composition having both enhanced broad spectrum
activity and low toxicity.
In general, the alkyl-N-sulfobetaine surfactant employed as a
zwitterion component of the composition can be written as: ##STR1##
where R is a higher alkyl having from 10 to 18 carbon atoms.
Illustrative of such alkyl-N-sulfobetaine are coco-N-sulfobetaine,
cetyl-N-sulfobetaine, stearyl-N-sulfobetaine,
isostearyl-N-sulfobetaine, oleyl-N-sulfobetaine, or mixtures of the
same.
The (1) alkyl-N,N-dimethylamine oxide, (2) dihydroxyethylamine
oxide, or (3) acylamido t-amine oxide component of the
aforementioned mixture, respectively has the structure: ##STR2##
where R.sub.1 is a higher alkyl from 10 to 18 carbon atoms, as for
instance, radicals such as decyl, undecyl, lauryl, tridecyl,
myristyl, cetyl, stearyl, isostearyl, oleyl or mixtures of the
same. Exemplary of the latter amine oxides are
decyl-N,N-dimethylamine oxide, lauryl-N,N-dimethylamine oxide,
stearyl-N,N-dimethylamine oxide, oleyl-N,N-dimethylamine oxide,
cocoamidotrimethylene-N,N-dimethylamine oxide,
stearylamidotrimethylene-N,N-dimethylamine oxide,
decyl-N,N-dihydroxyethylamine oxide, lauryl-N,N-dihydroxyethylamine
oxide, coco-N,N-dihydroxyethylamine oxide,
stearyl-N,N-dihydroxyethylamine oxide,
oleyl-N,N-dihydroxyethylamine oxide, and mixtures of the same.
In general, the protonating agent necessary to supply the required
pH to the overall composition is, for instance, any inert organic
or inorganic acid, such as hydrochloric acid, phosphoric acid,
sulfuric acid, citric acid, acetic acid, nicotinic acid, and the
like. A good operating pH range for the overall composition is 4.0
to 5.5 and, preferably, from about 4.7 to 5.2. The pH of an aqueous
solution comprising the above enumerated components of the
invention is determined by employing 0.5%, by weight, of active
components at a glass electrode to precisely define the acidity of
the composition.
In practice, each of the components of the overall composition
ranges widely from 0.1 part to 40.0 parts and the balance an inert
solvent, such as water or a lower monohydric aliphatic alcohol for
a total of at least 100 parts. Where water is employed, small
amounts of a lower alkyl alcohol may also be added thereto to
provide ease in formulation. The pH of the total composition is
then adjusted to the requisite pH by adding a suitable inorganic or
organic acid thereto. The composition can be employed as a solution
or as a spray, such as an aerosol spray utilizing commercially
available "Freon" fluorocarbon or equivalent propellant.
Advantageously, the compositions of the present invention possess
an extremely low toxicity exhibiting as an LD.sub.50 in
Swiss-Webster mice greater than four (4) grams per kilogram by
intraperitoneal or oral administration. Further, there are observed
a lack of primary irritation to the skin and less eye irritation as
compared with ordinary soap.
It has been found that the aforementioned compositions can be used
in a plurality of ways. For instance, when applied to pyogenic
wound infections, rapid healing is promoted. When used as an ear
douche, the compositions can relieve ear infections and eliminate
those mild microbial infections known as dandruff, crotch itch,
athletes foot and the like. As stated above and as shown in the
examples hereinbelow set forth, when the compositions of the
invention are employed as a general personal body wash, body odor
in the axillary and anal or genital areas in particular will be
inhibited for periods in excess of twenty-four (24) hours and
usually, will exhibit odor inhibition from seventy-two (72) to
ninety-six (96) hours.
In order to facilitate a further understanding of the invention,
the following examples are presented primarily for purposes of
illustrating certain more specific details thereof. The invention
is not to be deemed as limited thereby except as defined in the
claims. Unless otherwise noted, all parts and percentages are by
weight.
EXAMPLE 1
In this example, several compositions are prepared and used as a
body wash. Twelve panels each consisting of five men and five women
as subjects are selected and supplied with samples of the
compositions herein defined in Table I below. After twenty-four
(24) hours have elapsed since the panel members' last washing, each
is instructed to wash, noting particularly the axillary odor before
and after washing. The panel members are then examined during the
next twenty-four (24) hours and longer for the time span when
typical body odors develop. These times are then noted and recorded
in Table I below.
TABLE I
__________________________________________________________________________
Average Elapsed Panel Time Body Odor is No. Composition Detected
(hours)
__________________________________________________________________________
1. Cocoamido-N,N-dimethylamine oxide-12% actives in distilled water
(pH=7) 8 2. Cocoamido-N,N-dimethylamine oxide-12% actives in
distilled water - pH adjusted to 5.4 with citric acid. 10 3.
Coco-N-sulfobetaine-12% actives in distilled water - pH measured at
6.8 12 4. Coco-N-sulfobetaine-12% actives in distilled water - pH
adjustd to 5.4 with citric acid 12 5. Coco-N-sulfobetaine-6% in
distilled water, plus coco-N,N-dimethylamine oxide-6% in distilled
water at pH=6.4 12 6. Coco-N-sulfobetain-6% in distilled water,
plus cocoamido-N,N-dimethylamine oxide-6% in distilled water citric
acid-0.55% in distilled water at a pH=5. with citric acid 48-96 7.
Cetyl-N-sulfobetain-4% in distilled water, plus
myristyl/palmitic-N,N-dimethylamine oxide-6% in distilled water
adjusted to pH-5 with acetic acid 48-72 8. Cetyl N-sulfobetain-6%
in distilled water, plus Oleyl-N,N-dimethylamine oxide-6% in
distilled water, adjusted to pH=5.5 with citric acid 48-60 9. 70/30
Myristyl/palmitic-N,N-dimethylamine oxide- 12% in distilled
water-pH adjusted to 5.5 with citric acid 12 10.
Decyl-N,N-dimethylamine oxide-12% actives in distilled water-pH
adjusted to 5.2 with acetic acid 8 11. 70/30
Myristyl/palmitic-N,N-dimethylamine oxide-
6%+lauryl-N,N-dimethylamine oxide-6% in distilled water, adjusted
to a pH=5.2 with citric acid 10 12. 70/30
Myristyl/palmitic-N,N-dimethylamine oxide-
6%+coco-N-sulfobetaine-6% in distilled water, adjusted to a pH=5.1
with citric acid 36-48
__________________________________________________________________________
From the above table, it can be clearly seen that the compositions
of the present invention at the adjusted pH range cause a marked
improvement in body odor inhibition.
EXAMPLE 2
The relation between antimicrobial activity and control of body
odor is determined by subjecting each of the panel members of
Example 1 to additional washing tests employing the compositions of
Example 1. There are obtained the density of microbes in the
axillary area of each panelist by using a Rodac plate comprising
Tryptose soy agar with Tween.RTM.80 and lecithin to neutralize any
residual germicide. The panelist presses the plate for 30 seconds
to the axillary area of the armpit. The plates are then incubated
at 37.degree. C. for 24 hours and the number of colonies are
counted. The density in the colonies per square inch is next
calculated. The data obtained are noted in the table below and are
the average values of the subjects treated.
TABLE II ______________________________________ 0 12 24 48
Composition Hours after Hours after Hours after Hours after of
Example 1 washing washing washing washing
______________________________________ 1 1000 2300 TNC* TNC 2 1200
2500 TNC TNC 3 1400 2450 TNC TNC 4 1150 2650 TNC TNC 5 1350 2700
TNC TNC 6 450 800 1400 2200 7 380 650 1000 1400
______________________________________ *TNC means too numerous to
count the density is greater than 30000 colonies per square
inch.
EXAMPLE 3
There are admixed at 40.degree. C. stearyl-N-sulfobetaine (6.25
gm.), coco-N, N-dimethylamine oxide (13 gm.) citric acid (4.5 gm.)
and 125 gm. of distilled water. The pH of the mixture when diluted
to 0.5% actives is equal to 5.0.
The mixture is tested as a body shampoo and after 60 hours
subsequent to washing, the panel reported no evidence of body odor
in the axillary areas.
EXAMPLE 4
A mixture of stearyl-N-sulfobetaine (6.5 gms.),
coco-N,N-dimethylamine oxide (13 gms.), acetic acid (4.5 gms.), and
66 gms. of water, formed at 50.degree. C. and having a pH on
dilution is equal to 5.1, is employed as a body wash as in Example
3 above. Body odor is absent after seventy-two (72) hours.
Substituting hydrochloric acid for acetic acid in the above
mixture, similar results are noted.
EXAMPLE 5
There are admixed cetyl-N-sulfobetaine (2.5 gms.),
myristyl-N,N-dimethylamine oxide (5.5 gms.), citric acid (2.0 gms.)
and 87 gms. of water. The mixture is heated to 60.degree. C. and
the pH determined on dilution is 5.5.
As in Example 4 above, the mixture is used as a body wash to
determine axillary and pubic body odors. After 72 hours subsequent
to washing, no body odor is detected. Moreover, panel members with
dandruff report complete control of dandruff after two days' use
when washing once each day with the above composition.
EXAMPLE 6
A mixture of lauryl-N-sulfobetaine (5.2 gms.), 70/30
myristyl/palmitic-N,N-dimethylamine oxide mixture (5.5 gms.) citric
acid (0.7 gms.) and water (108 gms.) is heated to 35.degree. C. The
pH of the diluted solution is 5.4 and is used as a body wash. No
body odor is detected for seventy-two (72) hours after washing.
EXAMPLE 7
There are added at 30.degree. C. 6.2 gms. of coco-N-sulfobetaine,
6.2 gms. of 70/30 myristyl/palmitic-N,N-dihydroxyethylamine oxide,
5. gms. of isopropanol, 0.7 gms. of citric acid, and 92 gms. of
water. Upon dilution, the pH measured equals 5.5.
The mixture is used as a body shampoo and controls body odor for 48
hours after washing in all panel members.
EXAMPLE 8
There are admixed at 75.degree. C., 10 gms. of
cetyl-N-sulfobetaine, 10 gms. of coco-N-betaine, 42 gms. of 70/30
myristyl/palmitic-N,N-dimethylamine oxide, 15 gms. of isopropanol,
9 gms. of citric acid, and 550 gms. of water. There is obtained a
solution having a pH=5.0 on dilution and the preparation when used
as a body wash controls odor for more than 72 hours after
washing.
EXAMPLE 9
This example illustrates the formulation of a solid composition
comprising of 32 gms. of stearyl-N-sulfobetaine, 32 gms. of
myristyl/palmitic-N,N-dimethylamine oxide, 32 gms. of
2-stearyl-1-(ethyl-B-oxypropionic acid) imidazoline, 20 gms. of
isopropanol, 40 gms. of water and 6.3 gms. of citric acid. The
mixture is vigorously stirred and heated to a temperature of
80.degree. C. Resultant composition is then dried by evaporation
and cooled. There is recovered 110 gms. of a waxy solid product
having a pH equal to 5.0 at a 0.5% aqueous concentration.
The solid composition is employed as solid detergent for washing
and controls body odor for 48 hours after washing.
EXAMPLE 10
In this example there is prepared a spray composition. There are
admixed 0.1 gm. cetyl-N-sulfobetaine, 0.1 gm.
coco-N,N-dimethylamine oxide, 10 gms. isopropanol, and 0.02 gm. of
citric acid. The mixture is heated to 40.degree. C., cooled, and
admixed with 100 gms. of liquified butane in a suitable
container.
Resultant composition is sprayed under the armpits of several
panelists. Each reports underarm odor control for at least 48 hours
after use.
EXAMPLE 11
There are added to a suitable mixing vessel with stirring, 8 gms.
of coco-N-betaine, 8 gms. of stearyl-N-sulfobetaine, 16 gms. of
70/30 myristyl/palmitic-N,N-dimethylamine oxide, 3.3 gms. of citric
acid and q.s. to 250 gms. of water. Resultant mixture is stirred
vigorously and heated to 60.degree. C. for fifteen minutes.
Upon cooling, the pH of the mixture is found to possess a pH equal
to 4.7 on dilution.
Resultant composition is employed as a body wash following the
procedure of Example 2 above. After 12 hours, it is found by each
of five panelists that no body odor is detected and a bacterial
count of 190 colonies per square inch is obtained. After 36 hours,
no body odor is reported and the bacterial count rose to 600
colonies per square inch. The controls, however, in 36 hours all
reported detectable body odor and bacteria colonies too numerous to
count, when each of the controls constituting five panelists
employs a modified composition of this example in which citric acid
is omitted. The pH of the latter composition, on dilution, is
7.4.
Advantageously, the compositions of the present invention, and
particularly, as exemplified in each of the above examples, are
employed in successfully treating pyogenic infections. The
treatment consists of cleaning the wound by washing the same with
the composition of the invention and then covering the wound for
about 4 to 5 hours. In all cases, irritation and inflammation cease
within the four to five hour period, and most wounds exhibit
satisfactory healing within two to three days thereafter.
* * * * *